February 2016

The questions below are at the core of leading-edge research:

What determines* the location of the morphogen sources?

For Pom1 it is active transport of Tea4 via microtubules to the cell poles. Tea4 then forms a complex with Dis2 which removes the phosphor group(s) from Pom1. Un-phosphorylated Pom1 has a stronger binding affinity to the membrane, so that’s why it attaches preferentially at the pole. Now you can ask how the microtubules “know” where the poles are. I am not sure we know the answer, but one explanation could be that in a rod-shaped cell, the poles are the furthest from the cell center, where the microtubules start growing, so that’s simply the furthest they can go …

For Bicoid, another morphogen we studied a lot, its zone of production is determined by the localization of its mRNA, which is deposited at the anterior pole of the Drosophila embryo (by the nursing cells if I remember correctly).

What determines* the type of morphogen to be produced at a given source?

That’s ahard one. I don’t even know if there’s a “classification scheme” of morphogens into different “types”. The only thing that is clear that each system evolved towards robust functioning given the external constraints and the repertoire of molecular functions available at any given evolutionary time.

What determines* the timing for every morphogen source to start producing a given morphogen?

Also not simple: for Bicoid, the gradient forms quickly after egg lay. I guess the translation machinery (which is already part of the unfertilized egg) gets going as soon as “sees” the maternal mRNA, but I don’t know if there are any regulatory mechanisms in place the govern the timing. For Pom1, I believe its gradient is formed all the time, but, as cell size changes, this effects the gradient, as we discuss in our paper.

What determines* the amplitude of the morphogen gradients?

At steady state for a point like source with a production rate s_0 there is a simple answer to this: The amplitude is s_0 / sqrt(D*\alpha), where D and \alpha are the diffusion and decay constant, respectively (see eq.9 in attached paper). But for non-canonical systems the answers may vary. For example, in our model for Pom1 we should that its amplitude scales as Tea4 to the power 2/3.

(*) what’s the underlying mechanism and how does it work? 

So that’s the key question that we try to address for each system individually. Making progress depends, in my opinion, both on having excellent experimental approaches and skills, and innovative modeling that distill the essence of the system, neither making it too simple nor getting obscured by too many details that may be relevant but not essential.